The release of arachidonic acid (AA) by the lung and its conversion in situ to prostaglandins (PG) and prostaglandin metabolites (PGM) is well documented in man. Because of the marked pulmonary vasomotor properties, AA, PG, and PGM have been postulated as mediators of acute lung injury. We have recently detected pulmonary arterio-venous (A-V) differences in the serum concentrations of PGE2 and PGF2 alpha, and PGM's in man during acute adult respiratory distress syndrome (ARDS), the clinical focus of this project. Do PG's, AA, and PGM's initiate, aggravate or merely accompany the vascular and interstitial response to acute lung injury? We propose a systematic study of pulmonary A-V differences of AA, PG's, and PGM's in a large series of patients and, to a limited extent, in sheep under a wide range of clinical conditions which often involve stresses to the lung: ARDS, anesthesia, (with cardiopulmonary bypass, induced hypotension, hemodilution), surgery (thoracic, nonthoracic, burns) and medical intensive care (acute and chronic lung, renal, cardiac and liver disease). Serial paired blood samples will be drawn from indwelling pulmonary and radial arterial catheters. AA will be quantified by gas chromatography, PGE2, PGF2 alpha and PGM by radioimmunoassay. Samples will be drawn during experimental ovine respiratory distress induced by oleic acid, pulmonary microembolism, and endotoxin. These results will be correlated with clinical status, clinical laboratory values, and pulmonary function studies, and the results of special collaborative hemodynamic, coagulation and morphologic studies in order to better define prostaglandin alterations in the healthy and diseased lung of man.